TY - JOUR
T1 - Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non–small-cell lung cancer with high tumour mutational burden
T2 - patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial
AU - Reck, Martin
AU - Schenker, Michael
AU - Lee, Ki Hyeong
AU - Provencio, Mariano
AU - Nishio, Makoto
AU - Lesniewski-Kmak, Krzysztof
AU - Sangha, Randeep
AU - Ahmed, Samreen
AU - Raimbourg, Judith
AU - Feeney, Kynan
AU - Corre, Romain
AU - Franke, Fabio Andre
AU - Richardet, Eduardo
AU - Penrod, John R.
AU - Yuan, Yong
AU - Nathan, Faith E.
AU - Bhagavatheeswaran, Prabhu
AU - DeRosa, Michael
AU - Taylor, Fiona
AU - Lawrance, Rachael
AU - Brahmer, Julie
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/7
Y1 - 2019/7
N2 - Background: In the phase III CheckMate 227 study, first-line nivolumab + ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; ≥10 mutations/megabase). Aim: To evaluate patient-reported outcomes (PROs) in this population. Methods: Disease-related symptoms and general health status were assessed using the validated PRO questionnaires Lung Cancer Symptom Scale (LCSS) and EQ-5D, respectively. LCSS average symptom burden index (ASBI) and three-item global index (3-IGI) and EQ-5D visual analogue scale (VAS) and utility index (UI) scores and changes from baseline were analysed descriptively. Longitudinal changes were assessed by mixed-effect model repeated measures (MMRMs) and time to first deterioration/improvement analyses. Results: In the high TMB population, PRO questionnaire completion rates were ∼90% at baseline and >80% for most on-treatment assessments. During treatment, mean changes from baseline with nivolumab + ipilimumab showed early, clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; with chemotherapy, symptoms and health-related quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following induction (EQ-5D VAS). MMRM-assessed changes in symptom burden were improved with nivolumab + ipilimumab versus chemotherapy. Symptom deterioration by week 12 was lower with nivolumab + ipilimumab versus chemotherapy (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% confidence interval 2.4–22.5]), irrespective of discontinuation. Time to first deterioration was delayed with nivolumab + ipilimumab versus chemotherapy across LCSS and EQ-5D summary measures. Conclusion: First-line nivolumab + ipilimumab demonstrated early, sustained improvements in PROs versus chemotherapy in patients with advanced NSCLC and high TMB. Clinical trial registration: NCT02477826.
AB - Background: In the phase III CheckMate 227 study, first-line nivolumab + ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; ≥10 mutations/megabase). Aim: To evaluate patient-reported outcomes (PROs) in this population. Methods: Disease-related symptoms and general health status were assessed using the validated PRO questionnaires Lung Cancer Symptom Scale (LCSS) and EQ-5D, respectively. LCSS average symptom burden index (ASBI) and three-item global index (3-IGI) and EQ-5D visual analogue scale (VAS) and utility index (UI) scores and changes from baseline were analysed descriptively. Longitudinal changes were assessed by mixed-effect model repeated measures (MMRMs) and time to first deterioration/improvement analyses. Results: In the high TMB population, PRO questionnaire completion rates were ∼90% at baseline and >80% for most on-treatment assessments. During treatment, mean changes from baseline with nivolumab + ipilimumab showed early, clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; with chemotherapy, symptoms and health-related quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following induction (EQ-5D VAS). MMRM-assessed changes in symptom burden were improved with nivolumab + ipilimumab versus chemotherapy. Symptom deterioration by week 12 was lower with nivolumab + ipilimumab versus chemotherapy (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% confidence interval 2.4–22.5]), irrespective of discontinuation. Time to first deterioration was delayed with nivolumab + ipilimumab versus chemotherapy across LCSS and EQ-5D summary measures. Conclusion: First-line nivolumab + ipilimumab demonstrated early, sustained improvements in PROs versus chemotherapy in patients with advanced NSCLC and high TMB. Clinical trial registration: NCT02477826.
KW - Antineoplastic agents
KW - Carcinoma
KW - Ipilimumab
KW - Lung neoplasms
KW - Nivolumab
KW - Non–small-cell lung cancer
KW - Platinum-doublet chemotherapy
KW - Quality of life
KW - Surveys and questionnaires
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U2 - 10.1016/j.ejca.2019.05.008
DO - 10.1016/j.ejca.2019.05.008
M3 - Article
C2 - 31195357
AN - SCOPUS:85066924254
SN - 0959-8049
VL - 116
SP - 137
EP - 147
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -